Accepted Manuscript National Cancer Data Base Report on Pneumonectomy Versus Lung-Sparing Surgery for Malignant Pleural Mesothelioma Vivek Verma, M.D., Christopher A. Ahern, Ph.D., Christopher G. Berlind, Ph.D., William D. Lindsay, M.S., Sonam Sharma, M.D., Jacob Shabason, M.D., Melissa J. Culligan, R.N., M.S., Surbhi Grover, M.D., M.P.H., Joseph S. Friedberg, M.D., Charles B. Simone, II, M.D. PII:
S1556-0864(17)30687-1
DOI:
10.1016/j.jtho.2017.08.012
Reference:
JTHO 682
To appear in:
Journal of Thoracic Oncology
Received Date: 30 May 2017 Revised Date:
14 August 2017
Accepted Date: 15 August 2017
Please cite this article as: Verma V, Ahern CA, Berlind CG, Lindsay WD, Sharma S, Shabason J, Culligan MJ, Grover S, Friedberg JS, Simone II CB, National Cancer Data Base Report on Pneumonectomy Versus Lung-Sparing Surgery for Malignant Pleural Mesothelioma, Journal of Thoracic Oncology (2017), doi: 10.1016/j.jtho.2017.08.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
National Cancer Data Base Report on Pneumonectomy Versus LungSparing Surgery for Malignant Pleural Mesothelioma 1
2
2
2
RI PT
Vivek Verma M.D. , Christopher A. Ahern Ph.D. , Christopher G. Berlind Ph.D. , William D. Lindsay M.S. , Sonam 3 3 4 3 Sharma M.D. , Jacob Shabason M.D. , Melissa J. Culligan R.N., M.S. , Surbhi Grover M.D., M.P.H. , Joseph S. 4 5† Friedberg M.D. , Charles B. Simone, II, M.D. 1
M AN U
Shortened Title: Surgical Technique and Survival in Mesothelioma
SC
Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, USA 2 Oncora Medical, Philadelphia, PA, USA 3 Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA 4 Department of Surgery, Division of Thoracic Surgery, University of Maryland Medical Center, Baltimore, MD, USA 5 Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, USA
Disclaimers: None. This has never been presented or published before in any form. All authors declare that conflicts of interest do not exist.
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Funding: There was no research support for this study.
AC C
EP
†Corresponding Author: Charles B. Simone, II, MD University of Maryland School of Medicine Department of Radiation Oncology Maryland Proton Treatment Center 850 W. Baltimore St. Baltimore, MD 21201 Phone: 410-369-5215 Fax: 410-347-0870 Email: [email protected]
1
ACCEPTED MANUSCRIPT
ABSTRACT INTRODUCTION: Controversy exists regarding the optimal surgical technique for malignant pleural mesothelioma (MPM). We evaluated national practice patterns and outcomes of MPM treated with
RI PT
extrapleural pneumonectomy (EPP) versus lung-sparing extended pleurectomy/decortication (P/D).
METHODS: The National Cancer Data Base was queried for newly-diagnosed MPM patients undergoing EPP or P/D. Multivariable logistic regression ascertained clinical factors independently associated with
SC
P/D receipt. Kaplan-Meier analysis evaluated overall survival (OS) between cohorts; multivariable Cox proportional hazards modeling evaluated factors associated with OS. Survival was then evaluated
M AN U
between propensity-matched populations.
RESULTS: Overall, 1,307 patients (n=271 (21%) EPP, n=1,036 (79%) P/D) met criteria. Patients receiving P/D were older (p=0.028), whereas those undergoing EPP more likely lived in rural areas (p=0.044), farther from the treating facility (p=0.039), and treated at academic centers (p=0.050). There were no differences between cohorts in 30-day readmission or mortality (all p>0.05). Median OS in the EPP and
matching (p=0.540).
TE D
P/D groups was 19 versus 16 months (p=0.120); no differences were observed after propensity-
CONCLUSIONS: In the largest such analysis to date, findings from this contemporary cohort demonstrate that P/D comprised the majority of surgical procedures for MPM. Procedure type was influenced by
EP
sociodemographic and geographical factors, without observed differences in survival or postoperative
AC C
mortality/readmission rates between techniques.
Key Words: mesothelioma; radiation therapy; surgery; pneumonectomy; pleurectomy
2
ACCEPTED MANUSCRIPT
INTRODUCTION Malignant pleural mesothelioma (MPM) is a rare but highly aggressive malignancy associated with very poor prognosis. Surgery to attempt to achieve a gross macroscopic resection, with or without
RI PT
intraoperative adjuvant therapies, is considered an integral portion of multimodality therapy for most operable MPM patients.1-5 Whereas the historical surgical technique for MPM has been extrapleural pneumonectomy (EPP), this procedure is associated with notable peri- and postoperative adverse
SC
events and mortality.6 In efforts to address these issues, lung-sparing surgery in the form of extended pleurectomy/decortication (P/D) has more recently been utilized and is associated with fewer
M AN U
complications.7-8 Contemporary series evaluating the safety and efficacy of P/D-based multimodality management have demonstrated promising survival outcomes as well.9
Retrospective comparisons of overall survival (OS) between P/D and EPP have demonstrated that P/D yields equivalent1,10 or superior11-13 outcomes over EPP. However, concern exists that P/D is a
TE D
less oncologic procedure, and that it is more risky to deliver adjuvant radiation therapy following P/D than following EPP. Additionally, delineating the subpopulations benefiting from either surgical approach is less clear. This controversy is exemplified by United States guidelines changing multiple
EP
times over the past several years and currently recommending either EPP or P/D14, whereas the European Society of Thoracic Surgeons recommending that P/D “should not be proposed in a curative
AC C
intent”.15
This investigation is the largest such study for MPM evaluating surgical practice patterns and
outcomes for newly-diagnosed primary MPM using the National Cancer Data Base (NCDB) to determine the frequency of use of each definitive surgical procedure and identify if one technique results in superior OS relative to the other.
3
ACCEPTED MANUSCRIPT
MATERIALS & METHODS The NCDB is a joint project of the Commission on Cancer (CoC) of the American College of
RI PT
Surgeons and the American Cancer Society that consists of information regarding tumor characteristics, patient demographics, and patient survival for approximately 70% of the United States population.16-19 The NCDB contains information not included in the Surveillance, Epidemiology, and End Results (SEER)
SC
database, including details regarding use of systemic therapy. The data used in this study were derived from a de-identified NCDB file. The American College of Surgeons and the CoC have not verified and are
M AN U
neither responsible for the analytic or statistical methodology employed nor the conclusions drawn from these data. As all patient information in the NCDB database is de-identified, this study was exempt from institutional review board evaluation.
The NCDB Participant User File corresponding to mesothelioma (2004-2012) was utilized for this
TE D
study. Inclusion criteria for this investigation were patients with newly-diagnosed MPM that received EPP or P/D. Surgery type was defined by a thoracic surgeon with notable mesothelioma surgical experience (J.S.F.) as surgery of the primary intrathoracic site with codes 20-23, 30, 33, 40, 45-48, and 50
EP
for P/D and 55-56, 60, 66, 70 for EPP. Patients with all other types of surgery (including the following ambiguous surgical codes/labels: 12-13, 15, 19, 24 (local tumor destruction or excision, laser); 80
AC C
(resection, not otherwise specified); 90 (surgery, not otherwise specified)), those receiving surgery to the non-primary tumor site, or unknown surgery type were excluded. Patients without proper TNM staging were also removed, as were metastatic (stage M1) and/or palliative care patients. In accordance with the variables in NCDB files, information collected on each patient broadly included demographic, clinical, and treatment data. Statistical analysis was performed in R.20 Tests were two-sided, with a threshold of p
S1556-0864(17)30687-1
DOI:
10.1016/j.jtho.2017.08.012
Reference:
JTHO 682
To appear in:
Journal of Thoracic Oncology
Received Date: 30 May 2017 Revised Date:
14 August 2017
Accepted Date: 15 August 2017
Please cite this article as: Verma V, Ahern CA, Berlind CG, Lindsay WD, Sharma S, Shabason J, Culligan MJ, Grover S, Friedberg JS, Simone II CB, National Cancer Data Base Report on Pneumonectomy Versus Lung-Sparing Surgery for Malignant Pleural Mesothelioma, Journal of Thoracic Oncology (2017), doi: 10.1016/j.jtho.2017.08.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
National Cancer Data Base Report on Pneumonectomy Versus LungSparing Surgery for Malignant Pleural Mesothelioma 1
2
2
2
RI PT
Vivek Verma M.D. , Christopher A. Ahern Ph.D. , Christopher G. Berlind Ph.D. , William D. Lindsay M.S. , Sonam 3 3 4 3 Sharma M.D. , Jacob Shabason M.D. , Melissa J. Culligan R.N., M.S. , Surbhi Grover M.D., M.P.H. , Joseph S. 4 5† Friedberg M.D. , Charles B. Simone, II, M.D. 1
M AN U
Shortened Title: Surgical Technique and Survival in Mesothelioma
SC
Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, USA 2 Oncora Medical, Philadelphia, PA, USA 3 Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA 4 Department of Surgery, Division of Thoracic Surgery, University of Maryland Medical Center, Baltimore, MD, USA 5 Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, USA
Disclaimers: None. This has never been presented or published before in any form. All authors declare that conflicts of interest do not exist.
TE D
Funding: There was no research support for this study.
AC C
EP
†Corresponding Author: Charles B. Simone, II, MD University of Maryland School of Medicine Department of Radiation Oncology Maryland Proton Treatment Center 850 W. Baltimore St. Baltimore, MD 21201 Phone: 410-369-5215 Fax: 410-347-0870 Email: [email protected]
1
ACCEPTED MANUSCRIPT
ABSTRACT INTRODUCTION: Controversy exists regarding the optimal surgical technique for malignant pleural mesothelioma (MPM). We evaluated national practice patterns and outcomes of MPM treated with
RI PT
extrapleural pneumonectomy (EPP) versus lung-sparing extended pleurectomy/decortication (P/D).
METHODS: The National Cancer Data Base was queried for newly-diagnosed MPM patients undergoing EPP or P/D. Multivariable logistic regression ascertained clinical factors independently associated with
SC
P/D receipt. Kaplan-Meier analysis evaluated overall survival (OS) between cohorts; multivariable Cox proportional hazards modeling evaluated factors associated with OS. Survival was then evaluated
M AN U
between propensity-matched populations.
RESULTS: Overall, 1,307 patients (n=271 (21%) EPP, n=1,036 (79%) P/D) met criteria. Patients receiving P/D were older (p=0.028), whereas those undergoing EPP more likely lived in rural areas (p=0.044), farther from the treating facility (p=0.039), and treated at academic centers (p=0.050). There were no differences between cohorts in 30-day readmission or mortality (all p>0.05). Median OS in the EPP and
matching (p=0.540).
TE D
P/D groups was 19 versus 16 months (p=0.120); no differences were observed after propensity-
CONCLUSIONS: In the largest such analysis to date, findings from this contemporary cohort demonstrate that P/D comprised the majority of surgical procedures for MPM. Procedure type was influenced by
EP
sociodemographic and geographical factors, without observed differences in survival or postoperative
AC C
mortality/readmission rates between techniques.
Key Words: mesothelioma; radiation therapy; surgery; pneumonectomy; pleurectomy
2
ACCEPTED MANUSCRIPT
INTRODUCTION Malignant pleural mesothelioma (MPM) is a rare but highly aggressive malignancy associated with very poor prognosis. Surgery to attempt to achieve a gross macroscopic resection, with or without
RI PT
intraoperative adjuvant therapies, is considered an integral portion of multimodality therapy for most operable MPM patients.1-5 Whereas the historical surgical technique for MPM has been extrapleural pneumonectomy (EPP), this procedure is associated with notable peri- and postoperative adverse
SC
events and mortality.6 In efforts to address these issues, lung-sparing surgery in the form of extended pleurectomy/decortication (P/D) has more recently been utilized and is associated with fewer
M AN U
complications.7-8 Contemporary series evaluating the safety and efficacy of P/D-based multimodality management have demonstrated promising survival outcomes as well.9
Retrospective comparisons of overall survival (OS) between P/D and EPP have demonstrated that P/D yields equivalent1,10 or superior11-13 outcomes over EPP. However, concern exists that P/D is a
TE D
less oncologic procedure, and that it is more risky to deliver adjuvant radiation therapy following P/D than following EPP. Additionally, delineating the subpopulations benefiting from either surgical approach is less clear. This controversy is exemplified by United States guidelines changing multiple
EP
times over the past several years and currently recommending either EPP or P/D14, whereas the European Society of Thoracic Surgeons recommending that P/D “should not be proposed in a curative
AC C
intent”.15
This investigation is the largest such study for MPM evaluating surgical practice patterns and
outcomes for newly-diagnosed primary MPM using the National Cancer Data Base (NCDB) to determine the frequency of use of each definitive surgical procedure and identify if one technique results in superior OS relative to the other.
3
ACCEPTED MANUSCRIPT
MATERIALS & METHODS The NCDB is a joint project of the Commission on Cancer (CoC) of the American College of
RI PT
Surgeons and the American Cancer Society that consists of information regarding tumor characteristics, patient demographics, and patient survival for approximately 70% of the United States population.16-19 The NCDB contains information not included in the Surveillance, Epidemiology, and End Results (SEER)
SC
database, including details regarding use of systemic therapy. The data used in this study were derived from a de-identified NCDB file. The American College of Surgeons and the CoC have not verified and are
M AN U
neither responsible for the analytic or statistical methodology employed nor the conclusions drawn from these data. As all patient information in the NCDB database is de-identified, this study was exempt from institutional review board evaluation.
The NCDB Participant User File corresponding to mesothelioma (2004-2012) was utilized for this
TE D
study. Inclusion criteria for this investigation were patients with newly-diagnosed MPM that received EPP or P/D. Surgery type was defined by a thoracic surgeon with notable mesothelioma surgical experience (J.S.F.) as surgery of the primary intrathoracic site with codes 20-23, 30, 33, 40, 45-48, and 50
EP
for P/D and 55-56, 60, 66, 70 for EPP. Patients with all other types of surgery (including the following ambiguous surgical codes/labels: 12-13, 15, 19, 24 (local tumor destruction or excision, laser); 80
AC C
(resection, not otherwise specified); 90 (surgery, not otherwise specified)), those receiving surgery to the non-primary tumor site, or unknown surgery type were excluded. Patients without proper TNM staging were also removed, as were metastatic (stage M1) and/or palliative care patients. In accordance with the variables in NCDB files, information collected on each patient broadly included demographic, clinical, and treatment data. Statistical analysis was performed in R.20 Tests were two-sided, with a threshold of p
